tbuckley/cabot-search huggingface dataset:
A Public Health Ethics Framework for Populations with Limited English Proficiency
Authors: Samantha A. Chipman, Karen Meagher, Amelia K. Barwise
Journal: The American Journal of Bioethics (2023)

25.6 Million people in the United States have Limited English Proficiency (LEP), defined as insufficient ability to read, write, or understand English. We will (1) Delineate the merits of approaching language as a social determinant of health, (2) highlight pertinent public health values and guidelines which are most relevant to the plight of populations with LEP and (3) Use the COVID-19 pandemic as an example of how a breakdown in public health ethics values created harm for populations and patients with LEP. We define a framework to tease out public health responsibilities given some populations' limited proficiency in a society's predominant language. The American Public Health Association (APHA) public health ethics core values serve as a framework to interrogate current practices. We use the COVID-19 case to illustrate gaps between health policy and healthcare disparities experienced by populations with LEP.
Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders
Authors: Chanakyaram A. Reddy, Kristina Allen-Brady, Amiko M. Uchida, Kathryn A. Peterson, Alessandrina M. Hoffman, Rhonda F. Souza, Stuart J. Spechler
Journal: Clinical Gastroenterology and Hepatology (2023)
The prospects and challenges of chimeric antigen receptor T cell therapy for head and neck squamous cell carcinoma
Authors: Wei Liu, Xuemin Shen, Zhenhu Ren, Xi Yang
Journal: International Journal of Surgery (2023)

aDepartment of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China bCollege of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China cDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China d■■■■ Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai 200011, China. Tel.: +86 21 63162851. E-mail address: [email protected] (X. Shen). *Corresponding author. Address: Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai 200011, China. Tel.: +86 21 23271699. E-mail addresses: [email protected] (Z. Ren). *Corresponding author. Address: [email protected] (X. Yang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0/
Concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions: A systematic review and meta-analysis
Authors: Rory O'Sullivan, Stacey Bissell, Anna Hamilton, Andrew Bagshaw, Caroline Richards
Journal: Sleep Medicine Reviews (2023)

The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions (NDCs). A systematic literature search identified 31 studies that compare objective and subjective estimates of sleep parameters in autism, ADHD or rare genetic syndromes associated with intellectual disability. The meta-analyses revealed smaller mean differences and larger correlations indicative of greater concordance for parameters associated with sleep scheduling compared to parameters associated with sleep duration and night awakenings. Relative to objective measures, subjective measures produced: 1) greater estimates of total sleep time, sleep efficiency and time in bed; and 2) lower estimates of wake after sleep onset and number of night awakenings. Subgroup analyses also revealed differences in concordance between measurement comparison types (e.g., stronger correlations between actigraphy and sleep diaries, compared to actigraphy and questionnaires) and NDC diagnostic groups. The results predominantly replicate concordance trends observed in typically-developing samples, although some NDC-specific patterns of concordance were identified. This indicates that objective and subjective sleep measures retain broadly similar properties across populations, although researchers and clinicians should be cautious of the impact of NDC-related characteristics on sleep parameter estimates. These findings should inform sleep assessment design and the interpretation of sleep parameter estimates in NDCs, increasing the rigour of sleep parameter description across research and clinical settings.
Purinergic signalling in cancer therapeutic resistance: From mechanisms to targeting strategies
Authors: Wenhui Jia, Zhao Huang, Li Zhou, Yih-Cherng Liou, Francesco Di Virgilio, Henning Ulrich, Peter Illes, Wei Zhang, Canhua Huang, Yong Tang
Journal: Drug Resistance Updates (2023)

Purinergic signalling, consisting of extracellular purines and purinergic receptors, modulates cell proliferation, invasion and immunological reaction during cancer progression. Here, we focus on current evidence that suggests the crucial role of purinergic signalling in mediating cancer therapeutic resistance, the major obstacle in cancer treatment. Mechanistically, purinergic signalling can modulate the tumor microenvironment (TME), epithelial-mesenchymal transition and anti-tumor immunity, thus affecting drug sensitivity of tumor cells. Currently, some agents attempting to target purinergic signalling either in tumor cells or in tumor-associated immune cells are under preclinical or clinical investigation. Moreover, nano-based delivery technologies significantly improve the efficacy of agents targeting purinergic signalling. In this review article, we summarize the mechanisms of purinergic signalling in promoting cancer therapeutic resistance and discuss the potentials and challenges of targeting purinergic signalling in future cancer treatment.
Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement
Authors: Tania Gajardo, Mathilde Bernard, Marie Lô, Elisa Turck, Claire Leveau, Marie-Thérèse El-Daher, Alexandre Deslys, Patricia Panikulam, Constantin Menche, Mathieu Kurowska, Gregoire Le Lay, Lucie Barbier, Despina Moshous, Bénédicte Neven, Henner F. Farin, Alain Fischer, Gaël Ménasché, Geneviève de Saint Basile, Pablo Vargas, Fernando E. Sepulveda
Journal: Journal of Allergy and Clinical Immunology (2023)

<h3>Background</h3> The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in <i>TTC7A</i> have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. <h3>Objectives</h3> This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. <h3>Methods</h3> Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. <h3>Results</h3> We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. <h3>Conclusions</h3> These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.
Patient emergency health-care use before hospital admission for COVID-19 and long-term outcomes in Scotland: a national cohort study
Authors: Annemarie B Docherty, James Farrell, Mathew Thorpe, Conor Egan, Sarah Dunn, Lisa Norman, Catherine A Shaw, Andrew Law, Gary Leeming, Lucy Norris, Andrew Brooks, Bianca Prodan, Ruairidh MacLeod, Robert Baxter, Carole Morris, Diane Rennie, Wilna Oosthuyzen, Malcolm G Semple, J Kenneth Baillie, Riinu Pius, Sohan Seth, Ewen M Harrison, Nazir I Lone
Journal: The Lancet Digital Health (2023)

It is unclear what effect the pattern of health-care use before admission to hospital with COVID-19 (index admission) has on the long-term outcomes for patients. We sought to describe mortality and emergency readmission to hospital after discharge following the index admission (index discharge), and to assess associations between these outcomes and patterns of health-care use before such admissions.
Digital health equity for older populations
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2023)

July 11 marks UN World Population Day, which highlights the importance of global population issues. One such issue is population age and the pace of which it is increasing. WHO reported that, in 2020, the overall number of people older than 60 years, worldwide, outnumbered children younger than 5 years, although the COVID-19 pandemic has influenced mortality rates of older adults around the globe disproportionally. The overall increase is, in part, due to advances in medicine resulting in people living longer.
Wearable technology and the cardiovascular system: the future of patient assessment
Authors: Gareth J Williams, Abdulaziz Al-Baraikan, Frank E Rademakers, Fabio Ciravegna, Frans N van de Vosse, Allan Lawrie, Alexander Rothman, Euan A Ashley, Martin R Wilkins, Patricia V Lawford, Stig W Omholt, Ulrik Wisløff, D Rodney Hose, Timothy J A Chico, Julian P Gunn, Paul D Morris
Journal: The Lancet Digital Health (2023)

The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.
FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study
Authors: Christophe Tournigand, Thierry André, Emmanuel Achille, Gérard Lledo, Michel Flesh, Dominique Mery-Mignard, Emmanuel Quinaux, Corinne Couteau, Marc Buyse, Gérard Ganem, Bruno Landi, Philippe Colin, Christophe Louvet, Aimery de Gramont
Journal: Journal of Clinical Oncology (2023)

In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B).
Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair
Authors: Zhifeng You, Xu Gao, Xinyi Kang, Wen Yang, Tiandi Xiong, Yue Li, Feng Wei, Yan Zhuang, Ting Zhang, Yifu Sun, He Shen, Jianwu Dai
Journal: Bioactive Materials (2023)

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.
Stabilizing the neural barrier – A novel approach in pain therapy
Authors: Ann-Kristin Reinhold, Beate Hartmannsberger, Malgorzata Burek, Heike L. Rittner
Journal: Pharmacology & Therapeutics (2023)

Chronic and neuropathic pain are a widespread burden. Incomplete understanding of underlying pathomechanisms is one crucial factor for insufficient treatment. Recently, impairment of the blood nerve barrier (BNB) has emerged as one key aspect of pain initiation and maintenance. In this narrative review, we discuss several mechanisms and putative targets for novel treatment strategies. Cells such as pericytes, local mediators like netrin-1 and specialized proresolving mediators (SPMs), will be covered as well as circulating factors including the hormones cortisol and oestrogen and microRNAs. They are crucial in either the BNB or similar barriers and associated with pain. While clinical studies are still scarce, these findings might provide valuable insight into mechanisms and nurture development of therapeutic approaches.
A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal Cancer
Authors: Richard M. Goldberg, Daniel J. Sargent, Roscoe F. Morton, Charles S. Fuchs, Ramesh K. Ramanathan, Stephen K. Williamson, Brian P. Findlay, Henry C. Pitot, Steven R. Alberts
Journal: Journal of Clinical Oncology (2023)

Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease.
Development and Validation of a Prediction Model and Score for Transthyretin Cardiac Amyloidosis Diagnosis
Authors: Xabier Arana-Achaga, Cristina Goena-Vives, Iñaki Villanueva-Benito, Itziar Solla-Ruiz, Ainhoa Rengel Jimenez, Teresa Iglesias Gaspar, Iratxe Urreta-Barallobre, Gonzalo Barge-Caballero, Sara Seijas-Marcos, Eva Cabrera, Pablo Garcia-Pavía, María Teresa Basurte Elorz, Nerea Mora Ayestarán, Lucas Tojal Sierra, Maria Robledo Iñarritu, Ainara Lozano-Bahamonde, Vanesa Escolar-Perez, Cristina Gómez-Ramírez, Elisabete Alzola, Rubén Natividad Andrés, Jose Luis Francisco Matias, Javier Limeres Freire, Arola Armengou Arxe, Montserrat Negre Busó, Jesus Piqueras-Flores, Jorge Martínez-del Río, Jose Juan Onaindia Gandarias, Ibon Rodriguez Sanchez, Ramón Querejeta Iraola
Journal: JACC. Cardiovascular imaging (2023)

Although transthyretin cardiac amyloidosis (ATTR-CA) is often underdiagnosed, clinical suspicion is essential for early diagnosis.
Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access
Authors: Lorella Giovannelli, Elia Bari, Claudio Jommi, Fulvio Tartara, Daniele Armocida, Diego Garbossa, Fabio Cofano, Maria Luisa Torre, Lorena Segale
Journal: Bioactive Materials (2023)

Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as a potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked to the bioactive substances they release, collectively known as secretome. This paper provides an overview of the most recent research on the safety and efficacy of MSC-derived secretome and extracellular vesicles (EVs) in clinical (if available) and preclinical models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, acute ischemic stroke, and spinal cord injury. The article explores the biologically active substances within MSC-secretome/EVs, the mechanisms responsible for the observed therapeutic effects, and the strategies that may be used to optimize MSC-secretome/EVs production based on specific therapeutic needs. The review concludes with a critical discussion of current clinical trials and a perspective on potential future directions in translating MSC-secretome and EVs into the clinic, specifically regarding how to address the challenges associated with their pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence to Good Manufacturing Practices (GMP) guidelines, formulation, and storage, along with quality controls, access to the market and relative costs, value for money and impact on total expenditure.
Author correction to ‘Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system’ [Acta Pharm Sin B 7 (2017) 593–602]
Authors: Li-qian Ci, Zhi-gang Huang, Yu Liu, Zhe-peng Liu, Gang Wei, Wei-yue Lu
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].
CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer
Authors: Stéphane Fattori, Aude Le Roy, Jemila Houacine, Lucie Robert, Riad Abes, Laurent Gorvel, Samuel Granjeaud, Marie-Sarah Rouvière, Amira Ben Amara, Nicolas Boucherit, Carole Tarpin, Jihane Pakradouni, Emmanuelle Charafe-Jauffret, Gilles Houvenaeghel, Eric Lambaudie, François Bertucci, Philippe Rochigneux, Anthony Gonçalves, Arnaud Foussat, Anne-Sophie Chrétien, Daniel Olive
Journal: Cancer Research (2023)

Abstract Regulatory T cells (Treg) impede effective antitumor immunity. However, the role of Tregs in the clinical outcomes of patients with triple-negative breast cancer (TNBC) remains controversial. Here, we found that an immunosuppressive TNBC microenvironment is marked by an imbalance between effector αβCD8+ T cells and Tregs harboring hallmarks of highly suppressive effector Tregs (eTreg). Intratumoral eTregs strongly expressed PD-1 and persisted in patients with TNBC resistant to PD-1 blockade. Importantly, CD25 was the most selective surface marker of eTregs in primary TNBC and metastases compared with other candidate targets for eTreg depletion currently being evaluated in trials for patients with advanced TNBC. In a syngeneic TNBC model, the use of Fc-optimized, IL2 sparing, anti-CD25 antibodies synergized with PD-1 blockade to promote systemic antitumor immunity and durable tumor growth control by increasing effector αβCD8+ T-cell/Treg ratios in tumors and in the periphery. Together, this study provides the rationale for the clinical translation of anti-CD25 therapy to improve PD-1 blockade responses in patients with TNBC. Significance: An imbalance between effector CD8+ T cells and CD25high effector Tregs marks immunosuppressive microenvironments in αPD-1–resistant TNBC and can be reversed through effector Treg depletion to increase αPD-1 efficacy.
Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies
Authors: Rita Godinho, Alessandra Noto, Craig Fenwick, Athina Stravodimou, Sarah Hugelshofer, Solange Peters, Roger Hullin, Michel Obeid
Journal: Journal for ImmunoTherapy of Cancer (2023)

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1β, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.